Mitochondrial density contributes to the immune response of macrophages to lipopolysaccharide via the MAPK pathway

FEBS Lett. 2011 Jul 21;585(14):2263-8. doi: 10.1016/j.febslet.2011.05.049. Epub 2011 May 27.

Abstract

We investigated the role of mitochondrial reactive oxygen species (ROS) in the response of macrophages to lipopolysaccharide (LPS) using RAW 264.7 cells and their ρ(o) cells lacking mitochondria. Mitochondrial density, respiratory activity and related proteins in ρ(o) cells were significantly lower than those in RAW cells. LPS rapidly stimulated mitochondrial ROS prior to cytokine secretion, such as TNF-α and IL-6, from RAW 264.7 cells by activating the MAPK pathway, while the response was attenuated in ρ(o) cells. Exposure of ρ(o) cells to H(2)O(2) partially restored the secretion of cytokines induced by LPS. These results suggest that mitochondrial density and/or the respiratory state contribute to intracellular oxidative stress, which is responsible for the stimulation of LPS-induced MAPK signaling to enhance cytokine release from macrophages.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / physiology
  • Cell Line
  • Cell Respiration / physiology
  • Cytokines / metabolism
  • Lipopolysaccharides / immunology
  • Lipopolysaccharides / pharmacology*
  • MAP Kinase Signaling System / physiology*
  • Macrophages / cytology
  • Macrophages / drug effects*
  • Macrophages / immunology*
  • Mice
  • Mitochondria / metabolism*
  • Mitogen-Activated Protein Kinases / metabolism*
  • Nitric Oxide / metabolism
  • Oxidative Stress
  • Oxygen Consumption
  • Reactive Oxygen Species / metabolism

Substances

  • Cytokines
  • Lipopolysaccharides
  • Reactive Oxygen Species
  • Nitric Oxide
  • Mitogen-Activated Protein Kinases